• Kenneth J Moise, Leona E Ling, Dick Oepkes, Eleonor Tiblad, E J T Joanne Verweij, Enrico Lopriore, John Smoleniec, Ulrich J Sachs, Gregor Bein, Mark D Kilby, Russell S Miller, Roland Devlieger, François Audibert, Stephen P Emery, Kara Markham, Mary E Norton, Olga Ocón-Hernández, Pranav Pandya, Leonardo Pereira, Robert M Silver, Rory Windrim, James B Streisand, Jocelyn H Leu, Arpana Mirza, Valerie Smith, Lisa B Schwartz, May Lee Tjoa, Shumyla Saeed-Khawaja, Yosuke Komatsu, James B Bussel, and UNITY Study Group.
• From Dell Medical School, University of Texas at Austin, and the Comprehensive Fetal Care Center, Dell Children's Medical Center - both in Austin (K.J.M.); Janssen Pharmaceuticals, Cambridge, MA (L.E.L., J.H.L., A.M., V.S., L.B.S., M.L.T., S.S.-K., Y.K.); the Departments of Obstetrics (D.O., E.J.T.J.V.) and Pediatrics (E.L.), Leiden University Medical Center, Leiden, the Netherlands; the Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm (E.T.); the Feto-Maternal Unit, Liverpool Hospital, Liverpool, NSW, Australia (J.S.); the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University (U.J.S., G.B.), and the Department of Thrombosis and Hemostasis, Giessen University Hospital (U.J.S.) - both in Giessen, Germany; the University of Birmingham and the Fetal Medicine Center, Birmingham Women's and Children's NHS Foundation Trust, Birmingham (M.D.K.), and University College London Hospitals NHS Foundation Trust, London (P.P.) - all in the United Kingdom; the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center (R.S.M.), the Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College (J.B.B.), and NewYork-Presbyterian Hospital (J.B.B.) - all in New York; the Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, and the Department of Obstetrics, Gynecology, and Fertility, GZA Campus Sint-Augustinus, Wilrijk - both in Belgium (R.D.); Centre Hospitalier Universitaire Sainte-Justine Research Center, Université de Montréal, Montreal (F.A.), and Mount Sinai Hospital Toronto and University of Toronto, Toronto (R.W.) - both in Canada; UPMC Magee-Womens Hospital, Pittsburgh (S.P.E.); the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati Medical Center, Cincinnati (K.M.); the Department of Obstetrics and Gynecology, University of California, San Francisco, and Zuckerberg San Francisco General Hospital - both in San Francisco (M.E.N.); San Cecilio University Hospital, Granada, Spain (O.O.-H.); the Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland (L.P.); University of Utah Health, Salt Lake City (R.M.S.); and Streisand Biomedical Consulting, Wayland, MA (J.B.S.).
• N. Engl. J. Med. 2024 Aug 8; 391 (6): 526537526-537.

BackgroundIn early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.MethodsIn an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%).ResultsLive birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity.ConclusionsNipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).Copyright © 2024 Massachusetts Medical Society.

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